Dithiocarbamates and prevention of cadmium teratogenesis in the hamster.
Certain dithiocarbamates (DTC) have been reported to protect against cadmium (Cd)-induced lethality and to decrease Cd body burden. The present study evaluated the influence of sodium N-benzyl-D-glucamine dithiocarbamate, sodium N-di(hydroxyethyl)amine dithiocarbamate, sodium 4-carboxyamidopiperidine-N-dithiocarbamate, and sodium N-methyl-D-glucamine dithiocarbamate on Cd-induced teratogenesis in the hamster. When given as a single ip injection at 2.2 mmol/kg 15 min prior to iv CdCl2 (2 mg/kg), all of the DTC afforded significant protection against Cd-induced developmental toxicity and reduced kidney [Cd] in the dam. Maternal liver [Cd] was reduced with the glucamine and dihydroxyethyl amine analogs, but treatment with the piperidine failed to influence hepatic [Cd]. Pretreatment of the dams with DTC 24 hr prior to Cd challenge failed to protect against Cd-induced embryotoxicity, and provided minimal, if any, reduction in renal or hepatic [Cd]. Pretreatment with the N-methyl-D-glucamine congener 24 hr prior to Cd exposure increased embryolethality. The dose-time relationships found here suggest that pharmacologically effective levels of these DTC decline within 24 hr of treatment and that induction of metallothionein does not play a major role in DTC antagonism of Cd poisoning.
Hatori
A
A
Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan 84322.
Willhite
C C
CC
Jones
M M
MM
Sharma
R P
RP
D000818:Animals; D002105:Cadmium Poisoning / Q000188:drug therapy / Q000517:prevention & control*; D006224:Cricetinae; D005260:Female; D007668:Kidney / Q000002:abnormalities / Q000187:drug effects; D008099:Liver / Q000002:abnormalities / Q000187:drug effects; D008297:Male; D008431:Maternal-Fetal Exchange; D008647:Mesocricetus; D008668:Metallothionein / Q000378:metabolism; D011247:Pregnancy; D013859:Thiocarbamates / Q000494:pharmacology* / Q000627:therapeutic use
D013859:Thiocarbamates; D008668:Metallothionein